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PHYSIOLOGICAL  AND  PHARMACOLOG- 
ICAL  STUDIES  OF  THE    URETER.   III. 

RECAP 


BY  

DANIEL   R.   LUCAS,   M.A.,  M.D. 


COLUMBIA  UNIVFRR'Ty 

DEPARTMENT  OF  PHYSlPLO^v 

College  of  Physicians  and  Surgeons 
437  west  fifty  ninth  street 

NEW   YORK 


DISSERTATION 

Submitted   in   partial   fulfilment   of  the   requirements    for    the    Degree   of 

Doctor  of  Philosophy,  in  the  Faculty  of  Pure  Science, 

Columbia  University. 

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PHYSIOLOGICAL  AND  PHARMACOLOG- 
ICAL  STUDIES   OF  THE    URETER.    III. 


DANIEL    R.    LUCAS,    M.A.,   M.D. 


DISSERTATION 

Submitted   in   partial   fulfilment   of  the   requirements    for    the    Decree  of 

Doctor  of  Philosophy,  in  the  Faculty  of  Pure  Science, 

Columbia  I'ni vcrsity. 

Niav  York  Citv 

I'M,- 


Beprinted  from  the  American  Journal  of  Physiology. 
Vol.  XXII. —July  1,  1908.  — No.  II. 


PHYSIOLOGICAL  AXD   PHARMACOLOGICAL   STUDIES 
OF   THE  URETER.    III.1 

By  DANIEL  R.  LUCAS. 

[From  the  Laboratory  of  Biological  Chemistry  of  Columbia   University,  at  the 
College  of  Physicians  and  Surgeons,  New    Yorh.] 

CONTENTS. 

Page 

I.     On  transmission  of  pressure  from  the  bladder  to  the  kidney 245 

II.     Ureteral  pressure 250 

III.  Ureteral  pressure  and  renal  circulation 259 

IV.  Ureteral  pressure  and  the  flow  of  urine 263 

V.     biochemical  influences  on  ureteral  pressure 266 

VI.     Summary  of  general  conclusions 277 

I.  On  Transmission  of  Pressure  from  the  Bladder 
to  the  Kidney. 

Introductory.  —  It  is  often  said  that  "  distention  of  the  bladder 
seems  to  cause  congestion  of  the  kidneys  and,  when  frequent  and 
long  continued,  may  even  be  etiological  of  nephritis."  At  various 
times  clinicians  have  asked  whether  I  have  noticed  regurgitation 
of  urine  into  the  ureter  from  the  bladder. 

Although  I  have  been  unable  to  find  any  exception  to  the  state- 
ment that  the  so-called  uretero-vesicular  valve  is  normally  quite 
competent,  such  questions  as  the  one  mentioned  above  indicate  the 
existence  of  some  doubt  as  to  whether  pressure  in  the  bladder  may 
have  an  effect  on  the  kidneys  by  direct  transmission  through  the 
ureter,  or  only  by  indirect  nervous  influence.  Publication  of  some 
of  my  notes  regarding  this  matter  may  therefore  be  of  interest. 

Experimental. — My  first  observation  in  this  connection  was  made 
during  an  investigation  of  normal  ureteral  pressure  and  its  rela- 
tion to  the  peristaltic  movements  of  the  ureter  in  the  dog.2 

1  The  first  paper  was  published  in  this  journal,  1906,  xvii,  p.  392;  the  second 
t  appeared  in  the  New  York  medical  journal,  1907  (August  10). 

2  Lucas:  Proceedings  of  the  Society  for  Experimental  Biology  and  Medicine, 

],.  6l  |   also   S<  i<  nee,   1905,  xxi,  p.   721  ;    American  medicine,  1905,  ix.  p. 
741;  Medical   news,   1905,  Ixxxvii,  p.   87. 

245 


246  Daniel  R.  Lucas. 

In  that  series  of  experiments  a  cannula,  maintained  without  liga- 
tures and  not  materially  interfering  with  either  the  flow  of  urine 
or  the  peristalsis  of  the  ureter,  was  inserted  in  the  ureter  at  various 
locations  between  the  kidney  and  the  bladder.  It  was  connected 
with  a  water  manometer,  fitted  with  float  and  style  to  record,  on 
a  revolving  smoked  drum,  the  intra-ureteral  pressure  and  the  effect 
of  the  peristaltic  waves  on  that  pressure.  It  was  noted  that  if  a 
kink  in,  or  compression  of  the  ureter  below  the  cannula  prevented 
flow  from  the  ureter,  a  proportionate  increase  was  registered  in 
the  amount  of  intra-ureteral  pressure  and  the  number  of  peristaltic 
contractions,  —  results  that  confirmed  the  related  conclusions  of 
Sokoloff  and  Luchsinger.3 

An  unsuccessful  attempt  was  made  to  cause  a  more  rapid  rise 
in  intra-ureteral  pressure  than  was  obtainable  by  the  collection 
above  the  clamp  of  urine  secreted  by  the  kidney,  by  squeezing  the 
well-filled  bladder  with  the  hand.  This  was  done  in  a  number  of 
animals  and  frequently  repeated  in  the  same  animal.  In  all  but 
one  case  it  was  found  to  be  impossible  to  cause  in  this  way  in- 
creased intra-ureteral  pressure.  In  the  one  exceptional  case  the 
left  uretero-vesicular  valve  seemed  to  be  deficient.  The  right  valve, 
however,  was  entirely  competent.  The  force  exerted  on  the  bladder 
in  these  experiments  was  sufficient  in  each  case  to  overcome  the 
compressor-urethra  muscle  and  empty  the  bladder,  or,  when  the 
urethra  was  clamped,  to  burst  the  bladder.  In  the  ureter  in  situ, 
the  animal  being  narcotized  with  morphine,  the  rate  of  ureteral 
peristalsis  recorded  on  a  smoked  drum  was,  as  a  rule,  increased  by 
the  manipulation.  This  increased  contraction  was  apparently  caused 
by  nervous  influence  and  not  by  mechanical  distention  (Protocol 
No.  1). 

The  competency  of  the  uretero-vesicular  valve  was  noted  in  five 
different  experiments  in  which,  also,  the  ureteral  pressure  was  ob- 
served as  described  in  Protocol  No.  1.  The  nozzle  of  a  ten-ounce 
metallic  syringe  was  firmly  ligated  into  the  bladder  or  urethra,  and 
salt  solution  injected  until  the  bladder  burst,  without  affecting  the 
ureter  pressure  in  any  instance  (Protocol  No.  2).  In  five  perfusion 
experiments  the  recording  apparatus  was  not  attached,  the  ureter 
being  merely  inspected  and  palpated.  Pressure  exerted  as  described 
in  Protocol  No.  2  did  not  cause  dilatation  of  the  ureter.     In  all 

3  Sokoloff  and  Luchsinger:  Archiv  fur  die  gesammte  Physiologie,  1881, 
xxvi,  p.  464. 


Studies  of  the  Ureter. 


247 


these  experiments  the  freedom  of  flow  of  the  perfusion  fluid  through 
the  kidney  vessels  was  never  retarded  in  the  slightest  degree  by 
pressure  exerted  in  the  bladder  (Protocol  No.  3).  When  pressures 
of  20  to  40  cm.  of  water  were  produced  in  the  ureter  by  injection 
of  Ringer  solution  through  a  cannula  inserted  above  the  uretero- 
vesicular  valve,  the  venous  flow  from  the  kidney  was  markedly 
diminished  and  the  distention  of  the  ureter  could  be  plainly  seen 
and  palpated  (see  Fig.  1). 


FIGURE  1.  Upper  tracing,  drops  of  fluid  from  cannula  in  renal  vein.  Second  tracing  from 
top,  time  marked  in  seconds.  Third  tracing  from  top,  from  L  cannula  in  middle  por- 
tion of  the  ureter.  Fourth  tracing  from  top,  pressure  in  renal  pelvis  registered  through 
a  trocar  cannula.     Straight  line,  base  line  for  both  pressure  curves. 

A  series  of  experiments  were  performed  by  Dr.  Burton-Opitz 
and  myself,  in  the  Physiological  Laboratory  of  the  College  of 
Physicians  and  Surgeons,  on  the  circulation  of  the  blood  in  the 
kidneys  of  dogs  anesthetized  with  ether.  We  investigated  the  effect 
of  various  pressures  exerted  at  different  places  in  the  ureter,  and 
in  the  bladder,  on  the  rate  of  blood  flow  through  the  kidney,  as 
measured  with  the  Burton-Opitz  stromuhr.  It  was  found  that  the 
amount  of  pressure  necessary  to  almost  absolutely  suppress  the 
flow  through  the  kidney  when  exerted  in  the  ureter  varied  directly 
with  the  nearness  of  insertion  of  the  cannula  to  the  pelvis  of  the 
kidney.  That  variation  of  pressure  ranged  between  10  to  50  mm. 
of  mercury.4 

We  were  unable  to  note  any  change  in  the  rate  of  flow  of  blood 
through  the  kidney  in  the  experiments  in  which  we  recorded  the 

4  Bi  nz  and  Lucas:  Proceeding*  of  tin-  Society  for  Experimental 

Biology  and  Medicine,  1908,  v,  p.  44. 


248  Daniel  R.  Lucas. 

flow  from  one  kidney  while  special  pressure  was  exerted  in  the 
opposite  ureter.  The  results  obtained  by  pressure  in  the  bladder, 
which  was  accomplished  by  compressed  air  injected  at  different 
constant  pressures  through  the  urethra,  and  tried  in  increasing 
degrees  up  to  one  sufficient  to  burst  the  bladder,  were  also  negative. 

In  these  experiments  the  animals  had  previously  been  subjected  to 
various  other  tests :  to  prolonged  anesthesia  with  ether  and  chlo- 
roform; their  abdominal  contents  had  been  exposed  and  man- 
ipulated; and  often  the  renal  nerves  isolated  and  stimulated  by 
electricity.  Consequently  a  reflex  nerve  connection  between  blad- 
der and  kidney  or  between  the  two  kidneys  might  easily  have  been 
interfered  with  or  destroyed. 

In  all  experiments  in  which  the  flow  of  blood  through  a  kidney 
was  reduced  by  pressure  in  its  ureter,  the  blood  flow  rapidly  re- 
turned to  normal  when  the  pressure  was  released. 

When  the  bladder  was  removed  from  an  animal  and  water  in- 
jected into  it  through  the  urethra  until  it  burst,  no  leakage  was, 
as  a  rule,  produced  through  the  ureters. 

Conclusions.  —  The  results  of  these  precise  experiments  accord 
with  the  experience  of  many  a  boy  who  has  observed  that  a  pig's 
bladder  can  be  inflated  with  air  by  means  of  a  quill  inserted  in 
the  urethral  opening;  that  such  inflation  can  be  made  permanent 
by  ligation  of  the  urethra,  no  attention  to  the  ureters  being  re- 
quired; and  that  the  bladder  thus  distended  can  be  used  as  a 
football  for  days.  This  shows  without  doubt  that  the  normal 
uretero-vesicular  valves  are  entirely  competent,  and  that  they  wholly 
prevent  the  slightest  reflux  of  urine  under  any  degree  of  pressure 
which  can  obtain  in  the  bladder. 

Therefore,  as  has  been  suggested  above,  if  a  continuous  or  fre- 
quently distended  bladder  has  a  deleterious  effect  on  the  kidney, 
this  effect  must  be  brought  about,  not  by  any  direct  transmission 
of  pressure  from  the  bladder  to  the  kidney,  but  entirely  by  a  nervous 
mechanism. 

The  latter  will  be  considered  more  fully  in  a  later  research. 

Protocols.  1.  Dog;  weight,  24.56  kilos.  Milk  diet  for  twenty-four 
hours  before  the  beginning  of  the  experiment.  Morphine  (6  mg. 
per  kilo)  was  injected  hypodermically  at  9.45  a.  m.,  June  23,  1906. 
11  a.  m.  Animal  profoundly  narcotized.  A  trocar  cannula  was 
introduced   through   the   cortex    and   medulla    of    the   kidney    so 


Studies  of  the  Ureter.  249 

that  it  just  entered  the  renal  pelvis.     The  cannula  was  retained 
in  place  by  a  purse-string  suture  around  the  point  of  puncture  of 
the  capsule  of  the  kidney.     The  urine  aspirated  fresh  from  the 
bladder  was  injected  through  the  cannula,  and  the  patency  of  the 
cannula  and  the  ureter  ascertained.     An  improved  T  cannula  was 
inserted  in  the  lower  third  of  the  ureter.     Each  cannula  was  con- 
nected with  a  water  manometer  and  the  pressure  changes  were  re- 
corded by  means  of  an  Emerson  float,5  on  the  smoked  drum  of  a 
kymograph.     At  first   a  slightly  positive  pressure  was   recorded 
from  the  cannula  in  the  straight  portion  of  the  ureter,  and  also 
from  the  cannula  in  the  pelvis   of   the  kidney.     After  a  saline 
infusion  of  about  400  c.c.   in  the   femoral  vein,  the  amount  of 
secreted  urine  and  the  rate  of  peristalsis  were  increased,  but  the 
intra-ureteral  pressure  was  decreased.     The  bladder,   which  was 
distended  with  urine,  was  grasped  by  the  hand,  and  pressure  grad- 
ually exerted  until  the  sphincter  was  overcome  and  the  urine  re- 
leased.    This  Had  no  effect  on  the  pressure  recorded  by  either 
manometer,  but  the  irritation  of  the  bladder  called  forth  an  in- 
creased  peristalsis.      After   the   urine   had   escaped,   the   pressure 
recorded  by  the  cannulas  remained  about  the  same  as  previously. 
However,  the  variations  in  pressure  caused  by  each  peristaltic  con- 
traction were  not  so  great  for  a  time  as  they  had  been,  but  subse- 
quently the  waves  resumed  the  original  size. 
2.    Bull  dog;    weight,  16.8  kilos.     Morphine,  0.168  gram  at  9.40  a.  m., 
July  3,  1905.    Several  additional  small  doses  of  morphine  between 
10.40  and   11.20.     Two  cannulas  in  the  ureter  of  the  right  kid- 
ney:   one,  a  trocar  cannula  through  the  cortex  and  medulla  of 
the  kidney  into  the  renal  pelvis,  the  other  an  improved  T  can- 
nula, were  inserted  at  the  junction  of  the  upper  and  middle  thirds 
of  the  ureter.     A  straight  glass  cannula  was  inserted  in  the  left 
ureter  for  collecting  and  measuring  the  flow  of  urine. 

As  the  animal  seemed  to  exhibit  special  tolerance  for  morphine, 
a  small  amount  of  chloroform  was  administered  from  time  to  time. 
A  positive  pressure  of  2  cm.  of  water  was  registered  from  the 
straight  portion  at  times  when  the  chloroform  was  used,  which 
caused  retardation  of  the  muscular  action  of  the  ureter.0  As  the 
effeel  of  the  chloroform  wore  off,  the  pressure  in  the  pelvis  of  the 
kidney  increased,  and  the  pressure  in  the  straight  portion  of  the 
ureter  fluctuated  about  a  neutral  point.  One  gram  of  diuretin  in 
30  c.c.  of  physiological  salt  solution  was  infused   in  the   femoral 

'  Emerson:    Proceedings    of    the    Society   for    Experimental    Biology   and 
Medicine,    [904-1905,  ii,  p 

0  Lucas:  New  York  medical  journal,  August  10,  1907. 


250 


Daniel  R.  Lucas. 


vein.  It  gave  rise  to  a  flow  from  the  left  kidney  of  I  c.c.  of  urine 
in  eight  minutes.  The  tip  of  a  ten-ounce  hand  syringe  was  inserted 
at  the  urethro-vesicular  opening  and  securely  ligated  in  place.  The 
urethra  was  clamped,  and  salt  solution  was  injected  into  the 
bladder  until  the  bladder  burst.  No  increase  in  the  pressure  in  the 
ureter  was  shown  by  the  manometer. 
February  18,  1908.  —  The  kidney,  ureter,  and  bladder  of  a  dog  were 
collectively  removed.  The  cannula  and  recording  instruments  were 
adjusted  as  described  in  Protocol  No.  2.  Ringer  solution  was  per- 
fused into  the  renal  artery  at  a  constant  pressure  of  100  cm.  The 
fluid  from  the  renal  vein  was  collected  in  a  graduated  cylinder, 
and  record  was  made  of  the  time  which  elapsed  while  200  c.c.  were 
collected,  with  the  following  results : 

Tests  applied. 


The  urethral  outlet  was  clamped 
and  the  bladder  was  severely  squeezed 
with  the  hand. 

Ringer  solution  was  injected  into 
the  bladder  until  it  burst. 


Note.  —  The  tendency  of  the  vein  flow  gradually  to  decrease,  as 
shown  by  the  above  figures,  cannot  be  attributed  in  any  degree  to 
the  manipulation  of  or  pressure  exerted  in  the  bladder.  It  is  a 
phenomenon  observed  during  the  first  few  hours  of  all  kidney  per- 
fusion experiments,  and  has  been  accurately  described  and  charted 
by  Sollmann.7 

II.  Ureteral  Pressure. 

Introductory.  —  The  so-called  ureteral  pressure,  which  has  been  the 
subject  of  many  studies,  is,  as  pointed  out  by  Henderson,8  a  mis- 
nomer. In  the  investigations  of  the  so-called  ureteral  pressure  it 
was  not  the  pressure  exerted  by  the  ureter  that  was  studied,  but 
the  pressure  of  the  kidney  secretion  as  observed  by  a  manometer 
tied  in  the  ureter.  SokolofT  and  Luchsinger,  Henderson,  and  others 
observed  that  the  ureter  is  capable  of  contractions  sufficiently  strong 
to  overcome  a  very  considerable  intra-ureteral  pressure.  They  stated 
that  within  physiological  limits  the  rate  of  contraction  was  directly 

7  Sollmann:  This  journal,  1905,  xiii,  p.  249. 

8  Henderson:  Journal  of  physiology,  1905-1906,  xxxiii,  p.  175. 


Time. 

Fluid  from  the  vein. 

c.c. 

12.57  p.m. 

0.0 

1.11  p.m.  (14  min.) 

200.0 

1.29  p.m.  (IS  min.) 

200.0 

1.4S  p.m.  (19  min.) 

200.0 

2.09  p.m.  (20  min.) 

200.0 

2.29  p.m.  (20  min.) 

200.0 

Studies  of  the  Ureter.  251 

proportional  to  the  pressure.  I  have  seen  contractions  in  an  iso- 
lated piece  of  the  middle  portion  of  a  ureter  from  a  small  dog 
lift  a  pressure  column  of  Ringer  solution  92  cm.  high.  I  have  also 
recorded  graphically  contractions  under  a  pressure  of  86  cm.  of  the 
same  solution,  which  recurred  as  often  as  four  to  five  times  per 
minute  and,  without  decreased  frequency,  for  forty  minutes,  at 
the  end  of  which  time  the  pressure  was  diminished.  Pharmaco- 
logical experiments  were  satisfactorily  conducted  on  this  ureter 
for  some  time  thereafter. 

As  I  pointed  out  in  a  previous  paper,9  the  ureteral  peristalsis  is 
composed  not  only  of  wave  motions,  due  to  the  shortening  of  both 
longitudinal  and  circular  fibres,  that  travel  from  kidney  to  bladder, 
as  described  by  Engelmann,  but  also  of  wave  motions  in  at  least 
that  portion  of  the  ureter  contained  in  the  renal  pelvis,  which  are 
distinct  and  different  from  the  contractions  of  the  straight  portion. 
I  believe  that  further  research  will  justify  the  general  division  of 
the  ureter  into  the  following  two  portions  which  are  distinctly  unlike 
each  other  in  the  character  of  their  contractions  and  functions. 

1.  The  funnel-shaped  portion  above  the  isthmus  contained  in 
the  renal  pelvis  and  probably  partaking  of  the  nerve  distribution 
to  the  kidney. 

2.  The  straight  portion  extending  from  the  isthmus  to  the 
bladder,  which  may  be  subdivided  into  (a)  an  upper  third,  con- 
taining nerve  endings  in  its  wall;  (b)  a  middle  third,  deficient  in 
nerve  endings;  and  (c)  a  lower  third,  adjacent  to  the  bladder  and 
partaking  to  some  extent  of  the  nerve  distribution  to  the  bladder. 

I  have  often  found  that  the  ureter  is  capable  of  forcing  urine 
into  the  bladder,  even  when  sufficient  pressure  is  gradually  exerted 
in  the  bladder  to  burst  it,  no  rise  of  pressure  taking  place  in  the 
ureter  either  from  regurgitation  or  accumulation  of  urine  secreted 
by  the  kidney. 

Various  investigations  of  the  so-called  ureteral  pressure  have 
vn  that  pressures  varying  from  5  to  20  cm.  of  water  cause  vari- 
able effects  on  the  amount  and  constituents  of  the  urine.  Thus 
Steyrer10  found  that  pathological  closure  of  one  ureter  caused  an 
increased  flow,  diminished  specific  gravity,  and  lowered  freezing- 
point  of  the  urine.     Pfaundler  "  observed  an  increased  flow  in  three 

'   LUCAS  :  This  journal,  1906,  xvii,  p.  392. 

10  Sti  \  Ri  r  :  Beitrggezur  chemist  hen  Physiologie  und  Pathologie,  1902,  ii,  p.  312. 

II  Pfaundler:  lbid.s  1902;  ii,  \>.  336. 


252  Daniel  R.  Lucas. 

dogs  and  in  one  woman  under  similar  circumstances.  Schwarz  12 
noticed  that  pressures  of  10-25  cm.  of  oil  increased  the  flow  of 
urine,  but  that  greater  pressure  decreased  the  flow.  Cushny 13 
found,  without  exception,  that  a  pressure  of  19.5  cm.  of  water 
diminished  urinary  flow  in  rabbits.  Sollmann  14  concluded  from  his 
experiments  that  the  cause  of  the  increase  is  due  to  forces  vital 
and  not  mechanical. 

The  above-mentioned  observations,  in  the  light  of  my  own  ex- 
perience with  the  ureter,  lead  me  to  raise  this  question :  May  not 
the  living  ureter  antagonize  transmission  of  pressure  towards  the 
kidney?  I  believe  that  definite  conclusions  on  the  effect  upon  the 
kidney  of  pressure  exerted  in  the  ureter,  in  situ  or  uberlebend,  are 
unwarranted  before  we  know  definitely  how  internal  pressure  in- 
fluences the  ureter.  We  should  know  not  only  the  effect  in  the 
portion  below  the  isthmus,  but  also  in  the  portion  in  the  renal  pelvis, 
and  the  relation  of  the  pressure  in  these  two  portions  to  each  other, 
both  normally  and  when  artificially  produced. 

Before  proceeding  to  a  description  and  discussion  of  my  experi- 
ments intended  to  answer  this  question,  I  wish  to  emphasize  one 
point.  In  the  above  statement,  uberlebend  (i.  <?.,  surviving)  is  used 
advisedly.  The  maintenance  for  many  hours  of  vital  contractile 
activity  in  the  ureter  when  excised  has  made  it  a  very  satisfactory 
subject  for  the  study  of  many  points  regarding  involuntary  muscle 
tissue.  Not  long  ago  I  published  a  tracing  showing  the  effect  of 
caffein  on  an  excised  ureter  which  had  been  kept  in  physiological 
salt  solution  for  five  hours  after  the  animal  had  been  killed  by 
pithing.15  Subsequently,  in  studies  on  the  ureter  and  kidney  which 
had  been  excised  jointly  and  together  placed  in  warm  Ringer  solu- 
tion, contraction  waves  occurred  with  surprising  rapidity  and 
strength  during  perfusion  of  the  kidneys  with  Ringer  solution 
twenty-seven  hours  after  their  removal  from  the  animal.  These 
waves  were  graphically  recorded.  This  observation,  it  will  be  noted, 
was  made  on  the  second  day  of  the  experiment.  The  temper- 
ature of  the  bath  had  been  allowed  to  fall  to  that  of  the  room 
before  the  end  of  the  first  day  and  the  perfusion  fluid  had  been 
withheld  nineteen  hours.     Moreover,  the  peristalsis  had  been  en- 

12  Schwarz  :  Centralblatt  fur  Physiologie,  1902,  xvi,  p.  281. 

13  Cushny  :  Journal  of  physiology,  1902,  xxviii,  p.  431. 

14  Sollmann  :  This  journal,  1905,  xiii,  p.  276. 

15  Lucas  :  New  York  medical  journal,  August  10,  1907. 


Studies  of  the  Ureter.  253 

tirely  inhibited  at  the  end  of  the  first  day's  experiment  by  the  use 
of  barium  chloride,  my  intention  being  to  study  on  the  second  day 
the  effect  of  pressure  on  the  dead  ureter  and  kidney  as  compared 
with  that  on  the  living  ureter  and  kidney  on  the  previous  day.  Such 
observations  emphasize  the  vigorous  and  prolonged  vital  activity 
of  the  excised  ureter,  —  a  fact  in  harmony  with  similar  qualities 
of  the  excised  kidney,  as  has  been  pointed  out  by  Sollmann.16 

Experimental.  Methods.  —  The  present  experiments  were  made  on 
dogs  only.  As  a  rule  large  animals  were  selected.  The  ureter  was 
connected  with  a  recording  apparatus  by 

{A)  An  improved  cannula  made  of  two  portions,  introduced 
into  the  straight  segment  of  the  ureter.  That  part  of  the  cannula 
between  wfeich  the  vessel  wall  was  clamped  was  made  of  half 
cylinders,  the  perpendicular  cylindrical  portions  being  set  nearer 
one  end  of  each  than  the  other. 

(B)  A  trocar  with  a  blunt  obturator  was  introduced  into  the 
renal  pelvis  and  pushed  through  the  cortex  and  medulla  of  the 
kidney  so  that  it  just  entered  the  renal  pelvis. 

In  the  paper  on  the  peristalsis  of  the  ureter  two  tracings  were 
reproduced  for  the  purpose  of  illustrating  the  regularity  and  per- 
sistence of  ureteral  peristalsis.  At  that  time  no  significance  was 
attached  to  the  fact  that,  although  the  tracings  were  registered  by 
a  water  manometer,  the  curve  recorded  a  minimum  of  3  mm.  and 
a  maximum  of  5  mm.  positive  pressure  in  the  straight  portion  of 
the  ureter.  Throughout  the  entire  period  of  the  three  hours  that 
intervened  between  the  two  tracings,  a  constant  pressure  of  1 1  cm. 
of  urine  was  maintained  at  the  distal  end  of  the  ureter  17  connected 
with  a  vertical  glass  tube  from  the  upper  end  of  which  the  urine 
escaped.  In  that  particular  experiment  the  trocar  was  not  intro- 
duced into  the  renal  pelvis.  The  observation  suggests,  however, 
that  there  was  no  transmission  of  pressure  to  the  kidney  through  the 
ureter. 

In  fourteen  experiments  in  which  the  trocar  was  placed  in  the 
renal  pelvis  an  L  cannula  was  inserted  at  the  same  time  in  the 
straight  portion  of  the  ureter  at  various  locations  between  the 
isthmus  and  the  bladder,  and  pressure  was  exerted  in  the  outlet  can- 
nula 1  I  just  above  the  bladder)  by  one  of  the  following  three 
methods : 

ir'  SOLLMANN  :  This  journal,  1905,  xiii,  p.  243. 

17    I.u<  as  :  T'li is  journal,  I'joO,  xvii,  p.  yjj,  i  a  and  b. 


254 


Daniel  R.  Lucas. 


{A)   The  urine  was  allowed  to  collect  in  a  vertical  tube. 

(B)  The  outflow  was  blocked  by  clamping. 

(C)  Fluid  was  injected  through  a  T  cannula,  one  end  of  its 
horizontal  arm  transmitting  the  pressure  into  the  ureter,  the  other 
to  a  perpendicular  glass  tube  to  which  was  strapped  a  metre  stick 
to  facilitate  the  reading  of  pressure. 

Almost  without  exception,  in  the  experiments  that  were  conducted 
without  mishap,  pressure  up  to  15  cm.  did  not  cause  elevation  of 
the  pressure  recorded  from  the  straight  portion.  The  pressure  in 
the  pelvic  portion  almost  invariably  manifested  a  tendency  to  de- 
crease, although  under  these  conditions  contraction  waves  were 
seldom  recorded  from  the  pelvis.     When  pressure  higher  than  this 

was   exerted,   a   rise  of  pressure 
-  was  frequently  recorded  from  the 

straight  portion,  the  contraction 
waves  becoming  often  less  fre- 
quent, sometimes  more  frequent, 
at  which  time  the  tendency  to  a 
higher  pressure  record  from  the 
L  cannula  was  less  pronounced. 
Even  at  this  time  the  trocar,  as  a 
rule,  recorded  zero  pressure  in  the 
renal  pelvis.  Nevertheless  small, 
very  rapid  undulations  frequently 
began  to  appear  on  the  pelvic 
tracing  (Fig.  2),  and  if  the  pres- 
sure was  maintained  for  a  time, 
or  if  the  ureter  was  subjected  to  deleterious  conditions  such  as 
exposure  to  cold  or  desiccation,  or  if  chloroform  or  any  other  mus- 
cular depressant  was  administered,  the  pelvic  curve  showed  the 
tendency  to  development  of  a  positive  pressure,  while  the  straight 
portion  exhibited  larger  and  larger  waves,  at  less  frequent  intervals, 
on  which  smaller  waves  were  often  superimposed. 

When,  however,  the  pressure  was  permitted  to  continue  for  a 
sufficient  time  or  increased,  or  if  deleterious  drugs  were  allowed 
to  influence  conditions,  a  sudden  drop  of  pressure  in  the  straight 
portion  occurred  synchronously  with  an  abrupt  rise  in  the  pelvic 
pressure.  Both  pressures  returned  quickly  to  their  previous  levels, 
—  the  ureter  pressure  by  short,  step-like  ascents,  the  pelvic  pressure 
by  shorter  and  more  rapid  descents  (Fig.  3).     The  pelvic  pressure 


H- 


-4-4- 


Figure  2.  Lower  tracing,  time  in  seconds. 
Second  tracing,  base  line  for  pressure  in 
the  straight  portion  of  the  ureter.  Third 
tracing,  pressure  from  the  straight  por- 
tion of  the  ureter.  Fourth  tracing,  pres- 
sure from  the  renal  pelvis.  Fifth  tracing, 
base  line  for  pressure  in  the  renal  pelvis. 


Studies  of  the  Ureter. 


255 


usually  became  neutral,  the  curves  often  entirely  disappearing,  the 
phenomena  recurring  again  and  again,  tending  to  become  more  fre- 
quent ;  but  recurrence  was  by  no  means  regular.  Quite  often  the 
large  ureteral  curves  were  not  accompanied  by  the  large  pelvic  curves. 


fflY^Wl 


~M~~*~~~»*Y^™M~' — \r"\r^*~~ 


Figure  4.  Continuation  of  Fig.  3,  thirty 
minutes  later.  Lower  line,  base  line- 
Second  tracing  from  bottom,  from 
straight  portion  of  the  ureter.  Upper 
tracing,  from  renal  pelvis. 


Figure  3.  Lowest  tracing,  time  in  seconds 
and  base  line  for  the  pressure  in  the 
straight  portion  of  the  ureter.  Second 
tracing,  ureter  pressure  from  straight 
portion.  Third  tracing  represents  the 
base  line  for  the  pressure  curve  of  the 
renal  pelvis.  Fourth  tracing,  pressure 
from  renal  pelvis.  The  more  rapid 
oscillations  in  the  pelvic  curve  do  not 
show  in  the  figure. 


However,  large  pelvic  curves  never  appeared  under  these  conditions 
unaccompanied  by  decided  increase  in  the  size  of  the  ureteral  curves, 
but  large  pelvic  curves  could  be  induced  previous  to  the  appearance 
of,  or  unaccompanied  by,  the  large  curves  of  the  straight  portion, 
by  rapidly  infusing  into  a  femoral  vein  100  to  200  c.c.  of  warm 
physiological  salt  solution.  Following  the  large  pelvic  curve  thus 
produced,  the  curves  of  the  straight  portion,  as  a  rule,  became 
smaller  and  more  frequent  for  a  time,  but  subsequently  the  larger 
ascents  and  descents  took  place  again.  I  am  quite  sure  that  the 
drops  in  pressure  in  the  straight  portion  were  due  to  fatigue  and 
relaxation  of  the  ureter;  also  that  the  synchronous  rises  in  pres- 
sure in  the  pelvic  portion,  when  they  occurred,  were  due  to  reflux 
of  urine  into  the  renal  pelvis,  and  the  return  to  normal  pressure 
brought  about  by  the  recovery  and  natural  peristaltic  action  of  the 
two  portions. 

When,  however,  the  pressure  was  maintained  or  increased,  or  the 
action  of  deleterious  agents  brought  to  bear  on  the  ureter,  the  large 
curve  ra\  in  the  two  portions  became  higher  and  the  period 

of  n-turn  to  their  previous  levels  was  more  prolonged.  Subsequently, 
if   the   above-mentioned   deleterious   influences   were  continued,   the 


256  Daniel  R.  Lucas. 

ureteral  curves  became  more  rapid,  smaller,  and  regular.  The 
pressure  in  the  straight  portion  decreased  and  the  tendency  to  pro- 
duction of  large  curves  disappeared.  The  pelvic  pressure  increased, 
however,  the  curves  recording  it  becoming  larger  and  more  regular. 
These  curves  from  the  two  portions  continued  quite  regularly  for  a 
long  time,  but  occasionally  a  large  ascending  curve  occurred  in  the 
ureteral  tracing  synchronous  with  a  large  descending  curve  from  the 
pelvic  tracing  (Fig.  4).  This,  I  believe,  was  not  an  evidence  of 
further  fatigue,  but  a  manifestation  of  a  tendency  to  recovery,  and 
illustrates  what  I  think  occurs  under  normal  conditions,  but  which  I 
have  been  unable  to  demonstrate  with  my  crude  technique,  i.  e., 
the  tendency  of  the  ureter,  by  its  peristaltic  action,  to  dispel  or 
withdraw  from  the  renal  pelvis  and  kidney  all  pressure  that  would 
tend  to  arise  from  the  collection  of  urine  in  the  renal  pelvis,  per- 
haps even  in  the  uriniferous  tubules.  Not  infrequently,  as  before 
stated,  a  slight  degree  of  negative  pressure  was  recorded  from  the 
renal  pelvis  at  the  beginning  of  different  experiments  when  the 
ureter  wTas  contracting  actively.  Such  a  negative  pressure  would 
explain  also  why,  under  my  experimental  conditions,  no  pressures 
could  be  recorded  through  the  trocar  connected  with  a  water 
manometer,  for  the  exertion  of  a  counter  suction  caused  by  the 
column  of  water  in  the  manometer  would  draw  the  ureter  wall 
against  the  end  of  the  trocar  cannula  and  thus  effectively  prevent 
any  variations  of  pressure  from  being  transmitted. 

It.  may  be  advisable  to  mention  that  when  membrane  tambours 
were  used  in  place  of  water  manometers,  depressions  in  the  pelvic 
curve  were  frequently  noted  to  be  synchronous  with  contractions 
of  the  straight  portion  of  the  ureter,  even  when  fine  undulations 
were  not  transmitted  from  the  renal  pelvis.  It  seemed,  too,  that 
the  drop  in  pelvic  pressure  coincided  closely  (when  inspected  with 
the  naked  eye  at  the  time  the  tracings  were  being  recorded)  with 
the  longitudinal  motion  of  the  ureter. 

Analysis  of  some  of  the  experiments  on  animals  successfully  used  for 
study  in  situ  of  ureteral  pressure.  —  The  phenomena  produced  under 
these  experimental  conditions,  which  appear  to  be  constant  and 
which,  I  believe,  represent  closely  normal  states,  are  the  follow- 
ing: In  four  different  animals  there  was  a  slight  degree  of  nega- 
tive pressure  in  the  renal  pelvis.  At  that  time,  in  these  experiments, 
the  pressure  in  the  straight  portion  varied  from  o  cm.  to  10  cm. 
of  water,  positive.     In  other  experiments  a  negative  pressure  in 


Studies  of  the  Ureter.  257 

the  straight  portion  of  the  ureter  existed  to  the  extent  of  4  cm. 
The  difficulty  encountered  in  recording  negative  pressure  from  the 
renal  pelvis  was  also  met  with  in  recording  the  pressure  in  the 
straight  portion.  However,  the  shape  of  the  cannula  may  have 
furnished  a  condition  slightly  more  favorable;  its  rigid  half- 
cylindrical  walls  may  have  prevented  the  collapse  of  the  ureter  wall 
against  the  outlet  tube  to  the  manometer. 

In  two  experiments  showing  positive  pressure  in  the  renal  pelvis 
at  the  beginning  of  the  experiment  (in  one,  8  cm.,  in  the  other, 
6  cm.  pressure)  a  kink  in  one  of  the  tubes  was  subsequently  de- 
tected which,  on  removal,  allowed  the  pressure  to  fall  and  was 
without  doubt  the  cause  of  the  high  pressure  recorded.  In  four 
experiments  neither  negative  nor  positive  pressure  was  recorded. 
nor  were  any  contraction  waves  transmitted  until  positive  pressure 
was  caused  by  infusion  or  blocking  the  outflow  of  urine.  These 
results  demonstrated  that  the  connections  and  ureter  were  patent. 
I  am  inclined  to  believe  that  the  above-mentioned  neutrality  of 
pressure  was  due  to  the  fact  that  the  contractions  acted  so  efficiently 
in  carrying  the  urine  away  from  and  past  the  cannulas  that  there 
was  lacking  the  minimal  positive  pressure  necessary  for  the  pro- 
duction of  curves. 

As  a  rule,  increased  pressure  in  the  renal  pelvis,  whether  caused 
by  rapid  infusion  of  physiological  salt  solution  into  a  large  vein  of 
the  animal,  or  by  injection  with  a  syringe  through  the  wall  of  the 
rubber  tube  connection  between  the  trocar  and  manometer,  promptly 
increased  peristalsis.  The  latter  increased  directly  as  the  pressure, 
shortly  afterward  regaining  the  previous  frequency  and  extent.  The 
fact  that  in  the  straight  portion  the  peristaltic  rate  was  not  so  great, 
even  when  the  pressure  in  this  portion  was  still  rising,  after  the  injec- 
tion of  solution  had  been  discontinued,  suggests  that  the  flow  of  fluid 
along  the  ureter  under  such  conditions  may  also  tend  to  act  as  a  stim- 
ulus to  the  contractions  aside  from  that  induced  by  its  distention. 

Although  as  much  as  500  c.c.  of  physiological  salt  solution  was 

infused,  in  100  c.c.  amounts,  at  intervals  of  thirty  minutes  or  less, 

into  doj  hing  about  25  kilos,  the  ensuing  increased  flow  of 

urine  was  very  marked,  but   only  a  temporary  rise  of  pressure  in 

renal   pelvis  and   straight  portion   was  noted.     There  was,   of 

irse,  an  immediate  rise  of  blood  pressure.     In  the  renal  pelvis 

the   pressure   increase  occurred    simultaneously   with   the   infusion. 

earing  very  shortly  after  the  infusion  was  stopped.     Rise  in 


258  Daniel  R.  Lucas. 

the  straight  portion  was  somewhat  slower,  higher,  and  of  longer 
duration.  The  usual  stimulation  of  ureteral  contractions  during 
the  increase  of  pressure  was  noted,  and  it  was  found  that,  without 
exception,  the  pressure  quickly  returned  to  the  one  recorded  previous 
to  the  infusion.  In  fact,  the  saline  infusions,  under  conditions 
where  the  resistance  to  the  outflow  was  not  too  great,  seemed  to 
favor  peristalsis  more  decidedly  and  to  cause  a  diminution  of  intra- 
ureteral  pressure. 

Conclusions.  —  I  believe  these  experiments  indicate  very  strongly 
that  under  normal  conditions  the  intra-ureteral  pressure  remains  at 
zero.  The  amount  of  urine  in  the  ureter  that  ordinarily  is  necessary 
to  call  forth  peristalsis  is  probably  so  slight  that  it  causes  scarcely 
any  pressure  in  the  relaxed  ureter,  and  in  the  case  of  normal  per- 
istalic  contraction  directs  the  urine  into  the  bladder.  At  the  same 
time  a  tendency  to  the  production  of  negative  pressure  is  doubtless 
exerted  behind  the  mass  of  urine  that  proceeds  downward.  The 
flaccid  muscular  walls  would  be  collapsed  by  such  a  negative  intra- 
ureteral  pressure,  however.  A  mechanism  by  which  negative  pres- 
sure could  be  attained  to  an  appreciable  degree  in  the  straight 
portion  is  difficult  to  conceive.  In  the  renal  pelvis  conditions  are 
somewhat  different.  In  the  first  place  the  shape  of  the  ureter  above 
the  isthmus  becomes  more  and  more  flared.  This  portion  is  held  open 
by  its  attachment  to  the  firm  kidney  substance.  Again  this  portion 
is  abundantly  supplied  with  nerves.  From  my  observations  of  the 
action  of  this  portion  of  the  ureter,  I  am  inclined  to  believe  that 
here  conditions  prevail  which  are  less  favorable  to  accumulation  of 
urine  and  more  favorable  to  a  negative  pressure.  However,  there 
are  other  phenomena  than  those  already  mentioned  that  indicate 
highly  co-ordinated  and  purposeful  actions  of  this  portion. 

From  the  above  observations,  based  as  they  are  on  experimental 
study,  it  appears  that  the  ureter  is  specially  antagonistic  to  trans- 
mission of  pressure  towards  the  kidney.  The  portion  of  the  ureter 
above  the  middle,  unenervated  third,  is  apparently  even  more 
efficient  in  its  resistance  than  the  lower  portions.  The  pressure 
necessary  to  overcpme  this  action,  under  the  above-mentioned  con- 
ditions of  experimentation,  is  somewhat  above  that  produced  by  a 
30  cm.  column  of  water,  and  varies  naturally  with  the  duration  of 
application,  drugs  used,  exposure,  size  of  animal,  etc. 


Studies  of  the  Ureter.  259 

III.  Ureteral  Pressure  and  Renal  Circulation. 

Introductory.  —  The  experimental  results  already  recorded  here 
indicate  that  the  ureter  is  more  than  a  simple  conducting"  tube.  It 
not  only  carries  urine  away  from  the  kidney  and  discharges  it  into 
the  bladder,  but  by  its  peristalsis  it  also  prevents  collection  of  urine 
in  the  renal  pelvis,  thus  inducing  a  condition  favorable  to  continuous 
flow  from  the  tubules  and  spaces  of  Bowman's  capsules.  This  state 
of  affairs  brings  to  mind  a  much  studied  problem,  namely,  the 
nature  of  urinary  secretion. 

The  physical  phenomena  in  the  secretion  of  urine  have  recently 
been  extensively  studied  by  Sollmann,18  who  states  with  accuracy, 
"  a  knowledge  of  the  mechanical  phenomena  occurring  in  the  kidney 
would  seem  to  be  a  necessary  prerequisite  to  the  discussion  of  any 
theory  of  urine  secretion." 

It  is  obvious  that  any  influence  the  ureter  may  exert  on  the  kidney 
must  be  primarily  mechanical.  Therefore  I  have  made  a  study  of 
certain  mechanical  phenomena  in  urinary  formation,  with  the  ureter 
and  the  glomeruli  of  the  kidney  especially  in  mind  as  influencing 
factors. 

Experimental.  Methods.  —  In  these  investigations  I  have  followed 
in  a  general  way  Sollmann's  technique  for  perfusing  excised  kid- 
neys. I  am  indebted  to  Professor  Sollmann  for  important  sugges- 
tions in  this  connection.  My  experiments  differ  chiefly  from  his 
in  that  most  of  his  work  was  done  on  kidneys  in  which  the  vital 
action  was  very  largely  excluded  and  the  action  of  the  ureter  given 
little  attention,  while  I  have  tried  to  control  the  mechanical  phe- 
nomena to  as  large  a  degree  as  possible  by  removing  the  kidney 
and  ureter  from  the  animal,  at  the  same  time  endeavoring  to  main- 
tain the  vital  action  of  the  ureter. 

I  have  also  performed  a  number  of  perfusion  experiments  by 
Sollman's  technique  exactly,  in  order  to  test  his  methods.  Finding 
that  my  results  confirmed  his  observations  and  conclusions,  I  based 
many  of  my  tests  and  observations  on  his  analogous  data. 

The   vitality   of   the    kidney   and    ureter   is  very   persistent.  — 

Sollmann    presented    evidence    showing   that    a   certain    degree   of 

vitality  is  maintained  by  the  excised  kidney  for  many  hours.     His 

icriments  and  conclusions  applied  to  both  the  vitality  of  the  se- 

1*  Sollmann:  This  journal,  1905,  xiii,  p.  241. 


260  Daniel  R.  Lucas. 

cretory  epithelium  and  the  blood  vessels.  His  results  for  the  vessels 
are  classified  under  the  heads  :  ( i )  Dilator  reaction ;  (2)  Adrenalin 
reaction;  (3)  Hydrocyanic  acid  reaction.  Sollmann's  experimental 
results  show  that  the  vessels  maintain  vital  activity  to  some  degree 
two  days  after  excision. 

As  I  stated  before,  my  attention  has  been  directed  in  this  research 
to  the  vascular  system  of  the  kidney  and  to  the  ureter.  I  have  con- 
firmed the  results  of  Sollmann  on  the  vessels,  and  have  investigated, 
in  addition,  the  effects  of  the  following  on  the  ureter  and  on  the 
vessels  of  the  kidney:  adrenalin,  barium  chloride,  caffein,  diuretin, 
chloral,  chloroform,  magnesium  sulphate,  physostigmin,  atropin, 
pilocarpin,  cocain,  sodium  chloride,  oxygen,  carbon  dioxide,  cerium 
nitrate,  heat,  cold,  mechanical  irritation  and  electricity. 

My  observations  of  the  effects  of  the  above-named  substances  and 
conditions  will  be  taken  up  in  detail  in  the  fifth  section  of  this  paper. 
It  is  sufficient  to  state  here  that  the  vessels  of  the  excised  kidney 
and  the  ureter  are  susceptible  to  the  influence  of  drugs  for  many 
hours  after  excision. 

In  the  living  animal  there  are  many  conditions  that  influence  the 
renal  circulation.  The  following  technique  was  used  to  eliminate 
such  undesirable  influences  as  changes  in  general  blood  pressure  and 
nervous  control. 

The  animal  was  anesthetized  with  ether  or  the  skin  over  the 
femoral  artery  cocainized,  the  artery  exposed  and  cannulized,  and 
the  animal  bled  to  death.  An  incision  was  then  made  along  the 
linea  alba  from  ensiform  cartilage  to  symphesis  pubis  and,  by  trans- 
verse cuts,  extended  from  the  first  wound  through  the  abdominal 
muscles  to  the  dorsal  region,  passing  just  below  the  last  rib.  The 
ureter,  kidne)^,  and  bladder  were  exposed  by  retracting  the  other 
abdominal  viscera  in  warm  towels.  The  artery  of  the  kidney  to 
be  studied  was  exposed  and  cannulized  with  as  large  a  glass  cannula 
as  could  easily  be  inserted.  This  was  filled  immediately  with  warm 
Ringer  solution,  and,  by  means  of  a  ten-ounce  hand  syringe  joined 
to  the  cannula  by  a  short  piece  of  rubber  tubing,  the  kidney  vessels 
were  flushed  with  Ringer  solution  at  380  C.  until  the  vein  flow 
was  seen  to  be  clear.  The  vein  was  then  cannulized.  A  trocar 
cannula  was  introduced  and  retained  in  the  renal  pelvis,  and  an  L 
cannula  inserted  into  the  straight  portion  of  the  ureter.  If  the 
ureteral  flow  was  to  be  noted  or  the  effect  of  injection  into  it  studied, 
a  small  straight  glass  cannula  was  inserted  just  above  the  bladder 


Studies  of  the  Ureter.  261 

and  the  ureter  severed  below  the  cannula.  The  kidney  and  adjacent 
vessels  and  cannulas,  with  the  ureter,  were  removed  to  a  bath  of 
Ringer  solution  maintained  at  a  constant  temperature  of  38 °  C. ;  the 
artery  was  connected  to  a  perfusion  apparatus  consisting  of  a  20-litre 
bottle,  filled  with  Ringer  solution  and  fitted  with  a  Mariotte  tube  for 
maintaining  constant  pressure,  and  elevated  to  such  a  height  that 
an  injection  pressure  of  122.5  cm.  was  constantly  maintained.  A 
litre  flask  was  inserted  in  the  system  and  placed  in  a  water  bath, 
by  means  of  which  the  temperature  of  the  injection  fluid  could  be 
kept  constant.  A  thermometer  inserted  through  the  vertical  arm 
of  a  T  tube  just  proximal  to  the  point  of  injection  indicated  the 
temperature  of  the  perfusing  fluid  at  its  entrance  to  the  artery, 
which  temperature  was  maintained  at  380  C.  The  cannula  in  the 
straight  portion  of  the  ureter  and  the  one  in  the  renal  pelvis  were 
each  connected  to  a  membrane  tambour.  This  tambour  was  adjusted 
to  write  on  the  revolving  smoked  drum  of  a  kymograph  on  which 
the  time  was  marked  in  seconds,  and  the  rate  of  vein  flow  recorded 
in  drops  from  the  vein  cannula  allowed  to  fall  on  the  paddle  of  a 
Marey  tambour.  The  outlet  cannula  of  the  ureter  was  connected 
by  means  of  a  T  tube  to  a  perpendicular  tube  by  which  the  rate 
of  flow  or  the  resistance  of  flow  to  artificial  pressure  could  be  varied 
at  will. 

Results The  fifth  experiment  being  representative,  it  will  be 

used  as  illustrative  of  the  phenomena  thus  far  observed  by  this 
method.  In  this  experiment  the  outlet  cannula  of  the  ureter  was 
connected  with  the  perpendicular  tube  for  the  purpose  of  causing 
automatic  increase  of  pressure  at  the  distal  end  of  the  ureter. 

5.  February  18,  1908.  —  On  opening  the  arterial  clamp  the  kidney  be- 
qame  tense,  the  vein  flow  started  immediately  and  was  very  free 
—  twelve  drops  per  second.  The  pressure  in  the  renal  pelvis  rose 
abruptly  as  the  injection  fluid  entered  the  kidney.  The  pressure 
was  slight  and  showed  no  tendency  to  change  for  several  hours. 
No  contraction  curves  were  registered  from  this  portion  of  the 
ureter  until  later,  when  the  straight  portion  was  overcome  by  pres- 
sure and  fatigue. 

The  pressure  in  the  straight  portion  of  die  ureter  remained  at 
zero  for  ten  minutes,  no  peristaltic  waves  being  recorded.     At  the 

d  of  that  time  a  very  slight  rise  in  the  intra-ureteral  pressure  of 
the  straight  portion  was  noted,  when  the  peristaltic  waves  began 
abruptly  and  continued  at  the  rate  01  one  ill  ten  seconds,  tending 


262  Daniel  R.  Lucas. 

to  increase  in  rate  as  the  pressure  rose,  until  the  pressure  reached 
18  cm.,  when  the  curves  became  larger  and  slower. 

After  the  rapid  primary  flow  from  the  vein  had  reached  its 
maximum  there  was  a  gradual  decrease  as  the  time  of  perfusion 
advanced.  In  what  Sollmann  19  describes  as  the  third  stage  in  per- 
fusion of  the  excised  kidney,  at  the  point  where  the  vein  flow  re- 
mains almost  constant  (Fig.  5),  there  was  a  tendency  at  times 
when  the  ureter  action  was  most  efficient,  toward  an  increase  in  the 
vein  flow  (Fig.  6). 


4^%llW^ 


111«111^MJ1UU1)UB111MW1BU1WPWW- 


Figure  5.  Upper  tracing,  vein  flow  in  drops.  Second  trac- 
ing from  top,  time  in  seconds.  Third  tracing  from  top, 
ureteral  pressure  through  the  cannula  in  the  middle  of 
the  straight  portion.  Fourth  tracing  from  top,  pressure 
from  renal  pelvis.  Lowest  tracing,  base  line  for  both 
pressure  curves.  The  tracings  were  recorded  two  hours 
and  ten  minutes  after  perfusion  was  started.  The  num- 
ber of  ureteral  contractions  during  the  last  thirty  minutes 
of  this  time  averaged  56.1  per  ten  minutes  ;  the  vein  flow 
per  ten  minutes,  2056.8  drops  (124.4  c.c). 


Figure  6.  Same  as  Fig.  5, 
obtained  twenty  minutes 
later,  the  resistance  to  the 
ureteral  outflow  having 
been  increased  in  the 
meantime  from  5  to  10 
cm.  of  water.  Ureteral 
contractions  averaged  109 
per  ten  minutes.  Vein 
flow,  3840  drops  (228.5 
c.c.)  in  the  same  time. 


When  relaxation  and  inactivity  of  the  ureter  took  place,  there 
was  a  marked  decrease  of  the  pressure  in  the  straight  portion  of 
the  ureter  which  was  transmitted  to  the  pelvic  portion ;  at  the  same 
time  the  vein  flow  was  abruptly  reduced  from  10  to  less  than  1 
drop  per  second  (Fig.  7).  When  the  intra-ureteral  pressure  was' 
rapidly  increased  by  injection  of  Ringer  solution  through  the  out- 
let cannula,  the  primary  effect  of  the  increasing  pressure  in  the 
renal  pelvis  was  an  increased  vein  flow  (probably  due  to  expres- 
sion from  the  renal  vessels).  The  vein  flow  then  steadily  decreased 
as  the  pressure  increased.    When  a  maximum  pressure  of  38  cm. 

19  Sollmann:  This  journal,  1905,  xiii,  p.  249,  Fig.  2. 


Studies  of  the  Ureter.  263 

was  caused  in  a  period  of  twelve  seconds,  the  above-described 
phenomena  were  noted  in  spite  of  the  maintenance  of  this  maxi- 
mum pressure,  and  the  vein  flow  again  tended  to  increase  rapidly, 
but  in  the  succeeding  ten  minutes  did  not  attain  the  rate  noted 
previously  to  the  inauguration  of  the  pressure  (Fig.  8).  Again, 
if  the  above-mentioned  pressure  was  obtained  by  six  separate  in- 
jections at  intervals  of  ten  to  fifteen  seconds,  the  retardation  of  the 
vein  flow  was  much  less  distinct. 


IV.  Ureteral  Pressure  and  the  Flow  of  Urine. 

Introductory.  —  The  results  of  many  of  my  experiments  have  led 
to  the  conclusion  that  the  ureter  acts  in  an  antagonistic  manner  to 
pressures  toward  the  kidney,  and  that  this  action  of  the  ureter  not 
only  protects  the  kidney  from  pressure  caused  by  accumulation  of 
urine  in  the  renal  pelvis,  but  also  encourages  the  flow  of  blood 
throughout  the  kidney. 

Inasmuch  as  the  ureter  influences  by  its  action  or  non-action  the 
flow  of  blood  throughout  the  kidney,  the  ureter  must,  to  that  extent 
at  least,  influence  the  flow  of  urine.  In  some  of  my  experiments 
I  observed  that,  in  the  excised  ureter  and  kidney,  the  ordinary  re- 
lation between  them  was  somewhat  different  from  any  noted  when 
in  situ.  The  present  study  has  been  carried  out  on  the  kidney  and 
ureter  in  their  normal  relationships  in  order  to  determine  more 
intimately,  if  possible,  the  ureteral  influence  on  urinary  flow. 

Methods.  —  The  animal  was  kept  on  a  soft  or  liquid  diet  for 
several  days,  then  narcotized  by  hypodermic  injection  of  morphine, 
placed  in  a  dog-holder,20 'and  shaved  dorsally  from  the  last  rib  to 
the  crest  of  the  ileum  on  each  side.  An  incision  was  made  'from 
the  angle  between  the  last  rib  and  vertebral  column,  extended  down 
and  outward,  and  the  ureter  in  its  middle  or  lower  third  was  ex- 
posed retroperitoneally.  A  small  glass  cannula  was  introduced  into 
the  ureter,  which  was  severed  below  the  cannula  and  brought  to 
the  edge  of  the  wound,  the  wound  closed  by  interrupted  sutures, 
and  the  ureter  fixed  by  attaching  it,  by  a  slight  stitch  in  its  wall, 
to  the  surrounding  muscle.  The  urine  from  each  ureter  was  caught 
in  a  100  c.c.  graduated  cylinder  and  saved  for  examination.  The 
normal'  rate  of  flow  from  each  kidney  was  recorded.  When  this 
bad  been  satisfactorily  determined,  one  of  the  ureteral  cannulas 
20  Meyer:  This  journal,  1907,  xxix,  p.  906. 


264  Daniel  R.  Lucas. 

was  joined  to  a  perpendicular  glass  tube  of  small  calibre  by  the 
side  of  which  a  metre  stick  was  fastened.  The  other  cannula  was 
not  interfered  with,  nor  was  the  ureter  disturbed  by  the  adjustment 
of  connections.  Thus  the  effect  on  the  ureter  and  kidney  of  gradu- 
ally increasing  pressure  caused  by  the  secretory  activity  of  a  kidney, 
as  well  as  the  continuance  of  flow  from  each  kidney,  was  observed. 

Deductions  regarding  transmission  of  ureteral  pressure  to  the 
kidney  were  made  (a)  from  the  aspect  of  the  undulations  brought 
about  by  the  contractions  of  the  ureter  caused  in  the  vertical  tube 


Ui^uaniUJJliyUii^j_U_L 


Figure  7.  .         Figure  8. 

Figure  7.   Same  as  Fig.  5,  four  hours  after     Figure  8.   Same  as   Fig.  7  (later).     Peri- 
perfusion  was  started.     Peristalsis  infre-         stalsis   having    ceased,  ureteral  pressure 
quent   and   irregular,  ureter   relaxing   at         rapidly  increased  to  38  cm.  (of  water), 
times,  allowing  pressure  to  be  transmitted 
to  the  renal  pelvis.     Vein  flow  averaged 
1510  drops  (94.25  c.c.)  per  ten  minutes. 

through  which  the  pressure  was  exerted;  (b)  from  changes  in  the 
amount  and  composition  of  the  urine,  and  (c)  from  the  results  of 
post  mortem  examination  of  the  kidney. 

The  cannulas  were  maintained  in  the  ureters  two  or  three  days, 
at  the  end  of  which  time  they  ceased  to  remain  in  place,  because 
of  pressure  necrosis  of  the  ureter  due  to  the  retaining  ligature  at 
the  point  of  insertion  into  the  ureter.  The  animal  was  continuously 
protected  from  pain  by  small  though  sufficient  doses  of  morphine. 
Readings  were  made  on  each  day  for  periods  of  three  to  five  hours. 

Inasmuch  as  the  results  obtained  on  the  first  days  of  Experiment 
No.  2  are  typical,  they  will  be  cited  by  way  of  illustration. 

Results.  —  The  curves  of  Fig.  9  show  two  distinct  effects  of  pres- 
sure on  the  rate  of  flow,  i.  e.,  a  decided  increase  between  pressures 
of  2.5  and  25  cm.,  and  a  decrease  commencing  as  the  pressure  rose 
above  the  25  cm.  mark.  At  the  time  of  experimentation  it  was 
noted  that  while  the  flow  was  increased  as  the  pressure  rose  in  the 
perpendicular  tube  towards  the  25  cm.  mark,  the  meniscus  rose  and 
fell  in  a  rapid  and  regular  manner,   which  fluctuations,  'had  the 


Studies  of  the  Ureter.  265 

pressure  been  recorded  by  the  graphic  method,  would  have  given  a 
curve  of  the  character  shown  in  Fig.  2  (third  tracing  from  the 
bottom).  I  believe  the  intra-ureteral  pressure  conditions  repre- 
sented by  the  figure  referred  to  are  entirely  analogous  to  those 
attained  by  the  above-mentioned  method,  i.  e.,  the  pressure  exerted 
at  the  ureteral  outlet  is  not  transmitted  to  the  renal  pelvis,  there- 
fore does  not  act  on  the  kidney,  as  such,  although  the  stimulation 
of  the  ureter  may  have  an  indirect  effect  on  the  kidney. 

When  the  column  of  urine  nearly  reached  the  25  cm.  mark,  the 
oscillations  became  greater  in  extent  and  irregular  in  rate.  The 
same  pressure  also  caused  retardation  of  the  flow  of  the  urine.  The 
oscillations  of  pressure,  if  recorded  at  that  time,  would  have  exhib- 
ited a  curve  of  the  type  shown  in  Fig.  3  (second  tracing  from  the 
bottom).  The  oscillations  indicated,  I  think,  the  time  at  which  the 
ureter  muscle  was  succumbing  to  the  pressure  and  fatigue.  At  that 
point,  for  the  first  time,  pressure  as  such  exerted  at  the  outlet  of  the 
ureter  was  transmitted  through  the  ureter  to  the  kidney.  I  do  not 
believe  that  even  at  that  time  the  pressure  was  transmitted  in  its 
entirety.  Furthermore,  its  action  was  probably  only  for  brief 
periods. 

The  column  of  urine  continued  to  rise  and  oscillate  in  the  above- 
mentioned  manner  until,  after  a  time,  the  pressure  approached 
50  cm.,  when  again  the  type  of  oscillation  of  the  column  of  urine 
gradually  changed  to  that  represented  by  the  curve  in  Fig-.  4.  This 
curve  is  characterized  by  the  sudden  falls  of  pressure  and  the  more 
gradual  returns  to  the  previous  levels,  by  very  small  and  rapid  os- 
cillations, as  shown  by  the  second  curve  from  the  bottom  of  Fig.  4. 

As  the  pressure  increased  from  50  to  67  cm.  the  fluctuations  be- 
came smaller,  being  of  the  type  shown  on  the  ascending  portion 
of  the  curve  in  Fig.  3.  As  the  pressure  gradually  rose  during  this 
period,  fluctuations  of  greater  extent  occasionally  appeared,  as  is 
shown  in  Fig.  4. 

After  the  column  of  urine  reached  the  65  cm.  mark,  there  was 
no  fuvther  ascent  during  the  remaining  thirty-six  minutes  of  ob- 
servation, the  oscillations  in  the  pressure  tube  also  disappearing. 

Without  exception,  in  these  experiments  slight  pressure,  i.  c, 
from  2.5  t<>  25  cm.,  was  accompanied  by  increased  How  of  urine 
from  the  ureter  in  which  the  pressure  was  exerted.  The  results 
of  pr<  xperimenta  on  the  ureter,  compared  with  the  oscilla- 

tions of  the  fluid  in  the  pressure  tube  in  these  experiments,  make 


266 


Daniel  R.  Lucas. 


me  certain  that  pressures  exerted  in  the  ureter  between  2.5  and 
25  cm.  were  not  transmitted  as  such  to  the  renal  pelvis.  It  is 
probable,  however,  that  pressure  between  25  and  50  cm.  may  have 
been  transmitted  to  a  slight  degree  at  moments  of  relaxation  of  the 
ureter,  when  the  abrupt  drops  in  the  column  were  noticeable. 

The  behavior  of  the  ureter,  when  the  pressures  varied  between 
the  50  and  67  cm.  marks,  suggests  that  its  resistance  was  overcome, 
and  that  such  pressures  were  transmitted  almost  entirely  to  the 
kidney,  under  which  condition  there  was  absolute  stoppage  of  the 
urine  flow  from  that  kidney  during  a  period  of  eighteen  minutes. 

The  animal  was  then  returned  to  its  cage  at  4.30  p.  m.  (October 
12,  1907),  and  given  food  and  water  (500  c.c). 

The  curve  plotted  from  the  rate  of  ascent  of  the  urine  secreted 
in  the  vertical  tube  is  shown  in  Fig.  9. 

The  total  amount  of  urine  excreted  between  4.30  p.  m.  (October 
12,  1907)  and  9  a.  m.  (October  13,  1907)  was  175  c.c,  at  which 
time  the  animal  was  given  500  c.c.  of  water.  At  10  a.  m.,  0.044  §"m- 
of  morphine  were  injected  hypodermically.  At  10.45  A-  M->  35°  c-c- 
of  clear  material  was  vomited.  When  the  animal  became  thoroughly 
narcotized,  it  was  again  placed  in  the  dog-holder,  and  at  twelve 
o'clock  the  collection  of  urine  was  begun.  The  urine  from  the  leffe 
kidney  was  clear  and  reddish,  while  that  secreted  by  the  right 
kidney  was  clear  and  yellowish. 

The  rate  of  flow  from  each  kidney  was  recorded  as  follows : 


rime  of  observation. 

Urine  from 
right  kidney. 

Urine  from 
•  left  kidney. 

c.c. 

c.c. 

First  30  minutes 

6.20 

6.15 

Second  30  minutes 

4.80 

4.85 

Third  30  minutes 

4.00 

4.00 

Fourth  30  minutes 

2.90 

Fifth  30  minutes 

2.20 

3.50 

No 

albumin. 

Albumin  present, 

Sp. 

gr.  1  0245 

Sp. 

gr.  1.0277 

Remarks. 

The  urine  was  allowed  to 
flow  from  the  ureteral  can- 
nulas without  resistance. 

The  ureter  from  the  left 
kidney  was  attached  to  a  ver- 
tical tube ;  the  right,  as  above. 


V.  Biochemical  Influences  on  Ureteral  Pressure.21 

The  ureter  is  a  highly  specialized,  involuntary  muscular  organ, 
and  has  been  the  fruitful  subject  for  many  investigations  of  the 
myogenic  and  neurogenic  origin  of  automatic  muscular  contractions. 

21  Some  of  the  experiments  of  this  section  were  performed  in  the  Department  of 
Pharmacology  in  this  institution  under  the  direction  of  Dr.  A.  N.  Richards,  to 
whom  I  am  indebted  for  much  assistance. 


Studies  of  the  Ureter. 


267 


The  conclusions  of  such  studies  of  the  ureter  have  often  been  ap- 
plied to  the  beating  of  the  heart  and  to  the  movements  of  the  in- 
testines and  other  organs  largely  made  up  of  smooth  muscle  fibres. 
However,  the  extent  of  the  nerve  supply  of  the  middle  portion  of 
the  ureter  is  a  debatable  question  (Englemann,  Dogiel,  and  others). 
Protopow  made  an  extended  study  of  the  separate  existence  of  the 
requisite  elements  for  muscular  contractions.22  He  used  the  ureter 
as  the  subject  of  his  investigations,  which  were  both  histological  and 
biochemical  in  nature.  He  concluded  that  the  requisite  elements  for 
muscular  movements  are  found  separately  in  the  ureter  of  man  and 
the  higher  animals.     He  also  stated  that  stimulating  the  splanchnic 


X 

1 

i 

I 

. 

-1 

« 

^ 

u 

-8 

Figure  9.  The  curve  is  constructed  from  the  records  of  the  time  required  for  the  ex- 
creted urine  to  make  successively  an  advance  of  one  inch  in  the  vertical  tube  ;  increas- 
ing pressure  is  automatically  exerted  by  the  rising  column. 

nerves  has  a  motor  effect  on  the  ureter.  Fagge  23  pointed  out  that 
stimulation  of  the  hypogastric  nerve  has  a  motor  effect  on  the  por- 
tion of  the  ureter  adjacent  to  the  bladder. 

Of  more  purely  biochemical  nature  are  the  researches  of  Stern,24 
Hedon  and  Fleig,25  Manevitch,26  Pugliese,27  and  others,  in  which 
the  control  of  automatic  movements  of  the  ureter  by  various  cations 
and  anions  has  been  extensively  studied.  Hedon  and  Fleig  in- 
vestigated especially  the  effects  of  the  ions  which  are  found  in  the 
various  artificial  blood  sera. 

"   PROTOPOW:  Archiv  fiir  die  gesammte  Physiologie,  1897,  lxvi,  p.  1. 

23  FAGGE  :  Journal  of  physiology,  1902,  xxviii,  p.  304. 

24  STERN  :  These  de  (Geneva,  1903. 

26  HEDON  et  FLEIG  :  Archivea  internationales  de  physiologic,  1905-1906,  iii, 


P.  <r 


'»  Manevitch  :  Revue  metlicale  de  la  suisse  romande,  1907,  ncvii,  p.  585. 
'n  Pugliese:  An  hives  Italiennea  de  biologie,  1906-1907,  xliii,  p.  54. 


268  Daniel  R.  Lucas. 

Manevitch  divides  the  cations  which  affect  the  contractions  of 
the  ureter  into  three  groups:  (i)  Those  which  have  the  power  of 
preserving  to  the  highest  degree  the  automatic  contractions  of  the 
excised  ureter  (smooth  muscle  tissue),  e.  g.,  Na  and  Li;  (2)  Those 
which  depress  the  tonus  and  stop  the  rhythmic  and  automatic  func- 
tion of  smooth  muscle,  K,  NH4,  Mg,  Zn,  Cd,  Pb,  Co,  Ni,  Fe,  Mn, 
Cu;  (3)  Those  which  are  stimulants  to  the  tonus,  and  aid  develop- 
ment of  the  rhythmic  and  automatic  action  of  smooth  muscle,  fore- 
most among  which  are  Ba  and  Sr.  Ca,  according  to  Manevitch, 
occupies  a  special  place,  having  some  of  the  characters  of  barium 
and  strontium.  It  causes  a  development  of  deficient  automatic  con- 
tractions, and  renders  better,  and  more  energetic,  the  contractions  al- 
ready in  progress,  but,  on  the  other  hand,  often  tends  to  inhibit  or 
retard  the  rhythm. 

The  cations  Sr  and  Ba  are  conceded  by  Manevitch  to  be  antago- 
nistic, in  their  action  on  smooth  muscle  tissue,  to  those  of  the  second 
group  named  above,  i.  e.,  to  K,  NH4,  Mg,  etc.  Manevitch  also  states 
that  when  the  automatic  contractions  of  the  ureter  have  become 
greatly  diminished  after  hours  of  rction  in  solutions  containing  in- 
different cations  such  as  Na,  Li,  CI,  they  are  again  greatly  revived 
by  solutions  containing  Ba  or  Sr  cations. 

From  a  study  of  the  literature,  one  sees  that  the  activity  of  the 
ureter  must  be  greatly  influenced  by  chemical  as  well  as  nervous 
influences.  It  seems  probable,  then,  that  a  study  of  the  influence 
on  the  ureter  of  chemical  substances  which  occur  as  normal  con- 
stituents of  blood  and  urine  compared  with  the  effects  of  substances 
appearing  in  these  liquids  when  used  as  drugs  that  act  on  the  kidney 
(and  ureter?),  may  give  us  information  concerning  both  the  function 
of  the  ureter  and  the  action  of  drugs.  The  specific  influence  of 
drugs  on  the  ureter  in  a  normal  animal  cannot  be  precisely  con- 
trolled. However,  their  influences  can  be  determined  by  excising 
the  organ  and  placing  it  in  one  of  the  artificial  blood  sera  whose 
action  has  been  definitely  ascertained.  After  such  a  determination 
the  influence  of  drugs  under  ordinary  conditions  can  be  satisfac- 
torily recognized  with  due  regard  for  other  vital  processes  affected 
by  them. 

Experiments  on  the  excised  ureter.  Method.  —  Usually  a  cat  or 
small  dog  was  chosen,  which  was  anesthetized  with  ether,  or  bled  to 
death.  The  portion  of  the  ureter  to  be  studied  was  quickly  isolated 
and  removed  to  a  bath  of  warm  physiological  salt  solution,  where 


Studies  of  the  Ureter.  269 

the  adjustments  of  such  cannulas  and  apparatus  as  were  to  be  used 
in  the  particular  experiment  were  made,  one  of  the  three  following 
methods  of  procedure  being  used  : 

(A)  The  isolated  piece  of  ureter  was  ligated  at  both  ends,  one 
end  anchored  at  the  bottom  of  the  bath,  the  other  to  a  writing  lever 
which  traced  on  a  smoked  drum. 

(B)  The  anchorage  of  the  ureter  was  attained  by  inserting  the  end 
of  a  curved  glass  cannula  into  the  lumen  of  the  lower  end,  through 
which  warm  physiological  salt  solution  was  injected  for  the  pro- 
duction of  any  desired  intra-ureteral  pressure.  The  effects  of  the 
contractions  were  not  only  recorded  on  the  drum  as  in  method  A, 
but  could  also  be  noted  in  the  fluctuations  of  the  fluid  in  the  vertical 
pressure  tube. 

(C)  The  ureter  was  placed  horizontally  in  the  bath,  a  cannula  in- 
serted in  each  end  as  in  method  B,  and  a  myocardiograph  attached 
to  the  ureter  as  for  recording  contractions  of  the  heart. 

The  effect  of  barium  chloride  on  the  ureter  is  illustrated  by  Ex- 
periment 1,  which  was  performed  by  technique  A. 

1.  October  27,  1907.  —  Medium-sized  cat,  killed  by  decapitation.  The 
middle  third  of  one  ureter  and  a  section  of  the  small  gut  of  the 
same  length  as  the  section  of  ureter  were  excised,  ligatures  tied 
to  the  ends  of  each,  the  sections  anchored  at  the  bottom  of  a  beaker 
containing  Locke  solution  at  400  C.  (through  which  oxygen  bubbled 
constantly),  and  the  free  end  of. each  attached  to  a  spring  writing- 
lever  which  traced  on  a  revolving  smoked  drum. 

The  gut  began  to  record  contractions  immediately,  the  ureter 
remaining  perfectly  motionless  for  forty  minutes,  at  the  end  of 
which  time  1  c.c.  of  5  per  cent  barium  chloride  was  added  to  the 
40  c.c.  of  Locke  solution  contained  in  the  bath.  The  intestinal 
contractions  were  immediately  increased  greatly.  The  ureter  made 
its  first  contraction  thirty  seconds  after  the  addition,  which  was 
followed  by  contractions  occurring  every  twenty-five  to  thirty  sec- 
onds and  showing  for  a  short  time  a  tendency  to  become  stronger. 
Sometimes  the  excursion  of  the  recording  arm  was  very  great,  the 
succeeding  pause  being  correspondingly  lengthened.  Later  there 
was  a  tendency  for  two  contractions  to  occur  in  quick  succession 
or  for  a  second  to  occur  before  the  complete  relaxation  from  the 
first,  the  rate  of  contractions  increasing,  but  the  extent  of  contrac- 
tion becoming  less.  As  a  rule,  the  period  of  resl  following  a  double 
contraction  was  greater  than  that  following  a  single  contraction 
of  equal  extent.     The  contractions  continued  to  become  more  fre- 


270  Daniel  R.  Lucas. 

quent  and  less  in  extent  until  they  disappeared.     Subsequent  addi- 
tions of  barium  chloride  did  not  cause  additional  contractions. 

The  influence  o'f  adrenalin  on  the  isolated  ureter  as  tested  by  the 
same  method  was  exhibited  by  a  pronounced  increase  in  tonus  and 
contractility,  but  often  there  was  no  stimulation  of  the  rate  of  con- 
traction ;  in  fact  the  number  of  contractions  was  often  decreased,  as 
shown  in  Experiments  2  and  3,  protocols  of  which  are  appended : 

2.  December  6,  1907.  —  An  ox  ureter,  obtained  at  a  slaughter-house 
immediately  after  the  animal  had  been  killed  by  the  usual  method, 
was  placed  in  a  quart  jar  of  Ringer  solution  at  380  C.  and  carried 


Figure  10.    Lower  tracing,  time  in  ten  seconds.     Second  tracing,  contractions  of  the  ureter 
showing  the  effect  of  adrenalin  chloride. 

to  the  laboratory,  where  it  was  subjected  to  the  treatment  of 
method  B.  The  time  that  elapsed  between  the  killing  of  the  animal 
and  the  completion  of  all  manipulations  was  about  forty-five 
minutes. 

During  transportation  of  the  ureter  the  solution  in  which  it  was 
immersed  cooled  to  35 °  C. 

No  contraction  appeared  during  the  first  ten  minutes  after  the 
application  of  method  B,  at  the  end  of  which  time  1  c.c.  of  a  5  per 
cent  solution  of  barium  chloride  was  added  to  the  bath  of  500  c.c. 
of  Ringer  solution.  Fifty  seconds  later  the  first  contraction  was 
recorded.  It  was  followed  by  other  contractions  at  gradually  in- 
creasing intervals  of  from  two  seconds  to  two  minutes.  When  the 
contraction  rate  had  become  one  in  about  two  minutes,  0.2  c.c.  of 
1 :  1000  adrenalin  solution  were  added  to  the  bath,  whereupon  the 
rate  of  contraction  was  distinctly  decreased ;  but  the  line  that  was 
traced  when  the  ureter  was  at  rest  gradually  rose  for  fifteen 
minutes,  regardless  of  the  contractions  which  had  begun  to  show  a 
tendency  to  occur  in  groups  of  twos  or  threes  (Fig.  10). 
3.  December  13,  1907.  —  Small  dog-.  Etherized.  A  femoral  artery 
was  cannulized  and  the  dog  bled  to  death.  The  ureter  was  re- 
moved and  placed  in  500  c.c.  of  Ringer  solution.     Method  B  was 


Studies  of  the  Ureter.  271 

applied.  No  intra-ureteral  pressure  was  exerted,  and  only  one 
contraction  took  place  during  the  first  twenty  minutes,  which 
seemed  to  be  the  result  of  irritation  caused  by  handling  the  ureteral 
cannula.  The  intra-ureteral  pressure  was  then  increased  to  68  cm. 
Contractions  immediately  appeared,  and  recurred  fairly  regularly. 
The  pressure  was  lowered  to  50  cm.,  the  extent  of  contraction  be- 
coming greater  but  the  rate  remaining  about  the  same.  The  con- 
tractions continued  regularly  at  this  rate  for  forty-five  minutes, 
when  0.2  c.c.  of  1 :  1000  adrenalin  solution  was  added  to  the  bath 
of  500  c.c.  of  Ringer  solution.  The  contractions  continued  at  the 
previous  rate  for  thirty-five  seconds  longer,  then  eleven  contrac- 
tions occurred  in  the  succeeding  thirty-eight  seconds.  After  the 
last  of  these,  no  contraction  occurred  for  twenty-five  seconds, 
when  a  curve  resulted  which  was  composed  of  three  contractions 
and  reached  a  height  about  twice  that  of  any  previously  recorded. 
This  curve  was  followed  by  others  of  like  character  at  the  rate 
of  one  per  minute,  but  after  the  first  three  of  decreasing  size  and 
increasing  rate,  the  curves  showed  an  increasing  tendency  of  the 
contractions  to  occur  in  groups  ( Fig.  11). 


JUJUliJWil 


1 

^^_^jI_j_^-il-j1_L->_I-U-LJ_I-J-J  I   .LJ U_)ULJLJUJLLJUU 

Figure  11.  Lowest  tracing,  time  in  ten  seconds.  Second  tracing,  ureteral  contractions 
by  method  B  (where  an  intra-ureteral  pressure  of  68  cm.  Ringer  solution  prevailed). 
Third  tracing,  ;ntra-ureteral  pressure  had  been  reduced  to  50  cm.  at  the  mark  (,) 
02  c.c.  of  1  :  1000  adrenalin  solution  was  added  to  the  bath  of  500  c.c.  of  Ringer 
solution. 

In  other  experiments  with  the  same  technique,  where  the  con- 
tractions were  very  infrequent  or  entirely  absent,  a  slightly  larger 
dose  of  the  adrenalin  than  those  used  in  the  experiments  described 
in  the  preceding  protocols  caused  a  tonic  contraction  which  did  not 
show  any  tendency  to  relaxation  after  sixteen  minutes,  whereupon 
the  bath  was  changed  to  plain  Ringer  solution.  The  muscle  then 
gradually  relaxed,  returning  in  five  minutes  to  its  original  state. 

It  ^eems,  from  the  results  of  the  experiments  with  adrenalin,  that 
this  substance  increases  both  the  contractility  and  the  tone  of  the 
ureter  muscle. 


2J2  Daniel  R.  Lucas. 

Caffein  produced  phenomena  very  similar  to  those  caused  by 
adrenalin.  Diuretin  also  acted  in  a  similar  way.  Chloral,  chloro- 
form, ether,  and  magnesium  sulphate  were  distinctly  depressant, 
showing  at  times  a  slight  preliminary  irritation. 

In  the  experiments  with  the  excised  ureter  by  the  method  described 
above,  nicotin,  atropin,  muscarin,  and  physostigmin  gave  only  nega- 
tive results  (but  I  feel  confident  that  these  drugs  exert  definite 
influences  and  that  they  can  be  demonstrated  graphically  by  im- 
provement of  the  technique). 

The  ureteral  contractions  seemed  to  be  developed  less  satisfac- 
torily in  oxygenated  solutions  than  in  unoxygenated  ones. 

The  results  of  this  study  of  the  effects  of  drugs  on  the  excised 
ureter  warrant  the  following  conclusions : 

i.  Adrenalin,  caffein,  and  diuretin  increase  the  tone  and  con- 
tractility of  the  ureter  muscle. 

2.  Barium  chloride  increases  the  irritability  more  noticeably  than 
the  substances  of  the  first  group,  and  does  not  seem  to  have  such 
pronounced  influence  on  the  tone,  unless  it  is  to  depress  it. 

3.  Chloral,  chloroform,  ether,  and  magnesium  sulphate  exert  at 
first  slight  irritating  action,  but  later  cause  marked  depression. 

These  observations  on  the  excised  ureter  cannot  be  exactly  ap- 
plied to  the  complete  ureter,  however,  for  the  middle  third  was 
usually  employed  in  rthese  tests.  Nerve  influences  would  be  much 
less  prominent  in  this  portion  than  in  other  portions. 

Experiments  on  the  ureter  in  situ.      Method. DogS  were  Used  for 

all  of  these  experiments.  Chloroform  or  ether  was  employed  only 
for  the  purpose  of  studying  effects  upon  the  ureteral  peristalsis. 
The  animal  was  narcotized  with  morphine,  and  the  ureter  exposed 
by  an  incision  along  the  linea  alba  from  symphysis  pubis  to  ensi- 
form  cartilage.  The  abdominal  walls  were  then  retracted,  the  in- 
testines were  drawn  to  one  side,  and  the  viscera  as  well  as  the  rest 
of  the  animal  were  covered  with  warm  towels  and  cotton.  The 
kidney  was  exposed  by  another  incision  along  the  lower  border  of 
the  last  rib,  or  by  a  small  longitudinal  incision  directly  over  the 
kidney.  The  left  kidney  was  usually  selected  on  account  of  its 
lower  and  more  accessible  position. 

Graphic  representations  of  the  ureteral  movements  were  obtained 
as  usual  with  a  water  manometer,  the  undulations  of  the  column 
of  water  being  transmitted  by  means  of  a  float  and  style  to  a  re- 
volving drum.  The  connections  with  the  ureter  were  made  by  two 
methods : 


Studies  of  the  Ureter.  273 

{A)  By  introducing  into  the  ureter  a  cannula  which  is  a  modifica- 
tion of  the  Ludwig-Spengler  artery  cannula.  With  this  cannula  a 
much  smaller  incision  than  usual  is  required ;  no  ligation  being  neces- 
sary, the  propagation  of  the  muscular  wave  of  the  ureter  is  only 
slightly  interfered  with,  the  nutrient  vessels  of  the  ureter  can  be 
avoided,  and  the  nutrition  of  the  ureter  is  only  slightly  impaired. 

(B)  By  introducing  a  trocar  through  the  kidney  into  the  renal 
pelvis,  and  retaining  it  in  place  by  a  purse-string  suture  around  the 
point  of  puncture  of  the  capsule  of  the  kidney.  This  also  helped 
to  stop  bleeding,  which,  however,  was  surprisingly  slight.  A  small 
quantity  of  warm  salt  solution  or  urine  aspirated  fresh  from  the 
bladder  was  injected  through  the  needle;  thus  the  patency  of  the 
cannula  and  ureter  was  ascertained. 

In  connecting  the  cannulas  with  the  water  manometer  by  means 
of  narrow  glass  and  rubber  tubing,  urine  was  separated  from  the 
water  in  the  manometer  by  a  column  of  air.  Any  movement  of  the 
urine  caused  an  undulation  in  the  manometer.  These  undulations 
were  recorded  on  a  drum  by  means  of  an  Emerson  float. 

In  most  of  the  experiments  of  this  series  the  ureter  remained  in 
normal  connection  with  the  bladder.  In  some  experiments,  how- 
ever, the  ureter  was  severed  near  the  bladder,  the  urine  escaping 
into  the  abdomen  or  being  carried  out  of  the  body  by  a  glass  tube 
connected  with  the  cannula  in  the  ureter.  This  cannula  narrowed, 
of  course,  the  lumen  of  the  ureter,  and  thus  afforded  some  resist- 
ance to  the  flow  of  urine  out  of  the  ureter.  In  some  of  the  experi- 
ments the  urine  was  caused  to  drop  on  a  pan  connected  with  a 
Marey  tambour,  by  means  of  which  the  flow  of  urine  was  recorded. 

The  dose  of  morphine  varied  from  0.06  to  0.12  gram,  depending 
on  the  size  of  the  animal.  This  was  given  subcutaneously  sixty  to 
ninety  minutes  previous  to  the  operation.  All  experiments  were 
commenced  in  the  morning;  the  animals  had  not  been  fed  since 
the  previous  evening,  but  they  had  free  access  to  water. 

The  susceptibility  of  the  ureter,  in  situ,  to  the  various  substances 
used  in  this  study  seemed  to  be  much  greater  by  this  technique. 
Chloroform,  administered  in  the  respired  air,  caused  marked  de- 
e  "f  both  the  extent  and  frequency  of  the  contractions  of  the 
middle  part  of  the  ureter,  and,  if  continued,  completely  abolished 
them.  Sometimes,  when  the  administration  was  brief,  the  deteri- 
orating effect  did  nut  set  in  until  a  little  while  after  the  use  of  the 
anesthetic  was  discontinued.     Shortly  after  recovery  from  the  evil 


274  Daniel  R.  Lucas. 

effects  of  the  chloroform  in  some  of  these  cases,  another  period  of 
deterioration  set  in  as  a  second  after-effect. 

Frequently,  when  ether  was  suddenly  exhibited  in  the  respired 
air  (inhaled  per  nares,  not  by  tracheal  cannula),  a  temporary  change 
almost  instantaneously  appeared  in  the  curve  representing  the  per- 
istalsis of  the  ureter  in  the  renal  pelvis.  Sometimes  entire  cessation 
of  the  peristalsis  occurred,  which  phenomenon  could  also  be  elicited 
by  sudden  irritation  of  the  nostrils  with  a  probe,  —  an  observation 
very  strongly  suggestive  of  a  reflex. 

Moderate  doses  of  caffein  caused  various  effects  in  the  different 
parts  of  the  ureter,  the  portion  in  the  renal  pelvis  regularly  con- 
tracting in  a  somewhat  tonic  manner  and  causing  thereby  a  very 
pronounced  rise  in  the  pressure  for  a  short  time  in  that  part.  This 
pressure  appeared  to  be  attainable  through  the  agency  of  a  sphincter- 
like action  of  the  isthmus  of  the  ureter,  which  prevented  the  urine 
from  escaping.  The  pressure  in  the  straight  portion  did  not  exhibit 
a  simultaneous  change. 

Adrenalin  also  showed  a  tendency  to  disturb  the  normal  pressure 
relations  between  the  renal  pelvis  and  the  straight  part  of  the 
ureter.  It  caused  a  very  pronounced  positive  pressure,  very  much 
as  caffein  does. 

Barium  chloride  seemed  to  stimulate  the  contractions  of  both  the 
upper  and  lower  portions  without  the  same  tendency  to  cause  in- 
creased pressure  in  the  renal  pelvis. 

When  small  amounts  of  chloral  or  magnesium  sulphate  were 
injected  into  the  renal  pelvis,  only  a  direct  depression  was  shown. 

These  tests,  while  very  incomplete,  show  distinctly  that  the  ureter 
is  very  susceptible  to  the  action  of  drugs  administered  systemically 
as  well  as  directly.  The  experiments  with  chloroform  suggest  that 
there  may  be  a  double  action  of  drugs  on  ureteral  muscular  activity 
and  tone.  The  first  influence  on  the  peristalsis  was  exhibited  so 
promptly  after  the  administration  of  chloroform  had  been  begun, 
that  it  could  hardly  have  been  clue  to  chloroform  secreted  into  the 
urine  in  amounts  sufficient  to  affect  the  ureter  directly,  although 
it  seems  possible  that  the  circulating  blood  containing  the  drug 
might  have  some  such  effect.  When  the  chloroform  was  withdrawn, 
at  this  early  period,  the  very  pronounced  retardation  sometimes  did 
not  appear  until  the  animal  gave  indications  that  the  general  sys- 
temic action  was  wearing  off,  thus  increasing  the  impression  that 
drugs  act  on  the  ureter  not  only  while  circulating  in  the  blood,  but 
also  when  present  in  the  urine. 


Studies  of  the  Ureter.  275 

From  what  I  can  find  in  the  literature,  together  with  impressions 
obtained  in  my  own  studies  of  the  ureter,  it  seems  that  drugs  which 
exert  stimulating  action  on  the  ureter  also  appear  to  possess  diuretic 
power  to  a  somewhat  similar  degree.  I  think  I  am  correct  in  say- 
ing that  drugs  which  show  a  depressing  action  on  the  peristalsis 
of  the  ureter  also  often  exhibit  a  tendency,  when  administered 
systemically,  to  decrease  the  amount  of  urine.  These  conclusions 
suggest  that  stimulation  or  inhibition  of  ureteral  action  may  be  a 
factor  in  the  diuresis,  or  in  the  diminished  flow  of  urine,  caused  by 
drugs  having  the  above-mentioned  influences.  The  solution  of  this 
problem  presents  a  great  many  difficulties.  Nevertheless  it  should 
be  possible  to  gain  some  information  regarding  it  by  comparing  the 
effects  (on  the  volume  of  urine  eliminated  from  each  of  the  two 
kidneys  with  both  ureters  intact)  of  drugs  whose  influence  is  emi- 
nently diuretic  and  ureter-stimulating,  e.  g.,  caffein,  or  diuretin, 
with  the  flow  of  urine  from  each  kidney  after  the  ureter  of  one 
kidney  has  been  completely  eliminated. 

This  matter  was  tested  in  five  experiments  on  dogs  as  follows: 

Effects  of  drugs  on  the  comparative  flow  of  urine.  —  The  animals 
were  narcotized  with  morphine  and  the  ureters  exposed  only  at  their 
entrance  to  the  bladder.  A  small  straight  cannula  was  inserted  into 
each  ureter  at  this  location,  and  the  urine  collected  in  small  gradu- 
ated glass  cylinders.  The  normal  flow  was  noted  and  recorded  at 
regular  intervals. 

The  flow  from  the  kidneys  of  the  same  animal  was  found  to  be 
usually  quite  equal.  Infusion  of  150  to  200  c.c.  of  salt  solution 
caused  an  average  diuresis  of  20  per  cent  from  each  kidney  over  a 
period  of  thirty  minutes.  The  actual  amount  of  diuresis  varied  in 
the  different  animals.  Xo  attempt  was  made  to  maintain  uniform 
conditions  in  these  animals  previous  to  the  experiment.  The  diure- 
sis was  usually  quite  equal  from  the  kidneys  of  the  same  animal. 

When,  however,  1  gram  of  diuretin,  dissolved  in  50  c.c.  of  warm 
physiological  salt  solution,  was  infused  in  the  femoral  vein,  the 
increase  in  urine  from  each  kidney  was  equal  in  the  same  animal, 
but  varied  in  different  animals  from  between  250  to  300  per  cent. 
After  these  preliminary  tests  had  been  made  in  each  animal,  the 
ureter  from  one  of  the  kidneys  was  exposed  at  the  renal  pelvis,  and 
a  large  glass  cannula  which  tlared  out  considerably  a!  its  end,  so 
hold  the  portion  of  the  ureter  in  the  renal  pelvis  wide  open, 
was  inserted  and  retained  by  means  of  a  ligature.     Such  a  cannula 


276 


Daniel  R.  Lucas. 


prevented  any  influence  of  the  muscular  contraction  of  the  ureter 
on  the  flow  from  the  renal  pelvis  and  kidney.  (Great  care  was 
exercised  not  to  manipulate  the  kidney  or  interfere  with  the  renal 
vessels.)  The  urine  was  conducted  from  the  cannula  into  the 
graduated  cylinder,  care  being  taken  to  make  certain  that  the  de- 
gree of  resistance  to  the  flow  of  urine  from  each  cannula  was  equal. 
This  resistance  varied  from  between  2  to  8  cm.  in  the  different  ex- 
periments, after  all  manipulation  was  completed.     The  rate  of  flow 


2 

3 


0 


20 


40 


60 


80 


100 


Figure  12.  Upper  curve  gives  the  flow  from  the  left  kidney,  lower  curve  that  from  right 
kidney.  Cannula  in  renal  pelvis.  Ureteral  action  was  removed  from  the  right  kidney 
at  the  end  of  40  minutes  of  observation.  The  amount  secreted  was  recorded  at  the 
end  of  each  10  minutes.  0)  50  c.c.  salt  solution.  (2)  50  c.c.  salt  solution.  (3)  1  gm. 
diuretin  in  50  c.c.  salt  solution. 

from  each  kidney  was  again  observed,  and  as  a  rule  a  slight  decrease 
in  flow  was  noted  from  the  kidney  cannulized  at  the  renal  pelvis. 
Infusion  into  a  femoral  vein  of  50  to  100  c.c  of  physiological  salt 
solution  at  this  stage  frequently  failed  to  cause  an  increased  flow 
from  the  cannulized  kidney,  while  the  flow  from  the  kidney  with 
the  ureter  intact  showed  in  each  experiment  an  increase  of  at  least 
200  per  cent.  After  the  flow  from  the  kidney  with  its  intact  ureter 
had  returned  to  the  amount  eliminated  previous  to  the  infusion, 
and  the  urine  from  each  kidney  was  being  excreted  at  a  constant 


Studies  of  the  Ureter.  ,      277 

rate,  1  gram  of  diuretin  was  infused  in  50  c.c.  of  physiological  salt 
solution.  The  average  increase  of  the  flow  from  the  kidney  with 
intact  ureter  was  800  per  cent  for  the  first  ten  minutes,  falling  to 
200  per  cent  in  twenty  minutes.  From  the  cannulized  kidney  there 
was  only  a  125  per  cent  increase  in  the  first  ten  minutes  with  a 
return  to  the  normal  elimination  in  twenty  minutes  (Fig.   12). 

Although  the  damage  done  by  the  manipulation  when  inserting 
the  cannula  into  the  renal  pelvis  cannot  be  overlooked  as  an  influ- 
ence tending  to  decrease  the  amount  of  urine  excreted  by  that  kid- 
ney, the  above  observations  suggest  very  strongly  a  ureteral  influ- 
ence in  the  diuresis  caused  by  drugs  which  increase  the  muscular 
tone  and  activity  of  the  ureter. 

VI.  Summary  of  General  Conclusions. 

I.  If  continued  pressure  in  the  bladder  exerts  a  deleterious  effect 
on  the  kidney,  it  does  so  by  nervous  influence  and  not  by  direct 
transmission  of  pressure  from  the  bladder  to  the  kidney. 

II.  Even  under  the  artificial  conditions  of  experimental  study, 
the  intra-ureteral  pressure  tends  to  remain  approximately  neutral 
in  the  various  portions  of  the  ureter.  The  ureteral  pressure  is 
surprisingly  strong  and  efficient  when  called  upon  to  maintain  this 
intra-ureteral  condition. 

The  effect  of  the  antagonism  of  the  ureter  to  pressure  exerted 
in  it  must  be  carefully  taken  into  account,  especially  in  studies  of 
the  effects  of  artificial  pressure  through  the  ureter  on  the  kidney. 

The  vital  activity  of  the  ureter  is  extremely  persistent. 

HT.  Collectively  excised  kidneys  and  ureters  maintain  sufficient 
vital  activity,  when  the  kidney  is  perfused  with  warm  Ringer  solu- 
tion. In  permit  a  study  of  the  relation  of  the  mechanical  influence 
exerted  by  the  meter  on  the  circulation  of  the  kidney.  Under  these 
conditions  the  ureter  is  less  susceptible  to  pressure  influences.  There- 
fore it  is  not  so  efficienl  in  maintaining  low-pressure  conditions  in  the 
renal  pelvis  as  when  in  situ. 

Pressure  ill  the  renal  pelvis  lessens  the  circulation  through  the 
kidiK 

Sudden  increase  in  pressure  in  the  renal  pelvis  shows  more  pro- 
nounced checking  of  the  circulation  than  pressure  of  the  same  de- 
vhen  gradually  exerted. 

Retardation  of  renal  circulation  by  pressure  exerted  in  the  iciial 

nds  to  be  1  ompensated  for. 


278  Daniel  R.  Lucas. 

Ureteral  peristalsis  influences  renal  circulation  and  vice  versa. 

IV.  Stimulation  of  the  ureter  by  moderate  pressure  induces  an 
increased  flow  of  urine. 

Pressure  exerted  in  the  renal  pelvis  diminishes  the  flow  of  urine. 

A  pressure  of  67  cm.  of  urine  acting  in  the  renal  pelvis  causes 
distinct  damage  to  the  kidney,  as  shown  by  the  presence  of  blood 
in  the  urine,  and  by  the  macroscopical  appearance  of  the  kidney. 

V.  There  appears  to  be  a  ureteral  influence  in  the  diuresis  caused 
by  drugs  which  increase  the  muscular  activity  and  tone  of  the  ureter. 

Professor  William  J.  Gies  made  it  possible  for  me  to  inaugurate 
my  work  on  the  ureter.  Since  that  time  he  has  never  ceased  to  aid, 
encourage,  and  instruct  me  in  research  on  this  and  other  subjects. 
Whatever  scientific  or  clinical  advances  have  or  may  result  from 
my  efforts  in  research  are  directly  dependent  upon  his  interest  and 
assistance. 


BIOGRAPHICAL 

Daniel  Ralph  Lucas  resided  in  La  Fayette,  Indiana,  from  [88 1 
to  1898  inclusive.  He  received  a  public  school  education  in 
La  Fayette.  In  1898  he  enlisted  in  the  160th  Regiment,  Indiana 
Volunteer  Infantry,  in  which  he  served  during  the  war  with 
Spain.  He  was  Captain  of  the  Hospital  Corps  at  Purdue 
University,  1901-1902,  and  Major  of  the  1st  Batallion  and  Ranking 
Cadet  officer  there  in   1902- 1903. 

At  various  times  from  1901  to  1904  he  held  the  position  of  pre- 
scription clerk  at  Hogan  and  Johnson's,  and  Bartlett's  pharmacies 
in  La  Fayette,  Indiana,  and  at  Stork's  pharmacy  in  Chicago,  111. 

He  has  been  assistant  and  subject  in  the  Private  Research 
Laboratory  of  Dr.  C  A.  Herter  at  various  times  since  1905;  also 
assistant  chemist  and  a  subject  in  an  investigation  by  the  U.  S. 
Dept.  of  Agriculture,  of  the  effects  of  sodium  benzoate  in  food  on 
human  metabolism. 

He  was  University  Fellow  in  Biological  Chemistry,  Columbia 
University,  1907-  1908,  and  is  Fellow  of  the  Alumni  Association 
of  the  College  of  Physicians  and  Surgeons,  Columbia  University 
(1908- 1 909.) 

He  has  practiced  medicine  in  New  York  City  since  1907. 

DEGREES    RECEIVED 

From  Purdue  University — Ph.  G.,  1901;  B.S.,  1903. 
From  Columbia  University — M.A.,  1906;  M.D.,  1907. 

PUBLICATIONS 

Studies  of  the  peristalsis  of  the  ureter  of  the  dog  by  the 
graphic  method.  American  Journal  of  Physiology,  1906,  xvii, 
P«  392. 

Clinical  aspects  of  recent  developments  in  the  physiology 
and  pharmacology  of  the  ureter.  New  York  Medical  Journal ',  [907 
( August  io). 

Pharmacological  studies  of  magnesium  salts.  VI.  (With 
S.  J.  Meltzer).  The  Journal  of  Experimental  Medicine \  1907,  iii, 
p.  298. 

Physiological  and  pharmacological  studies  of  tin-  ureter.  III. 
Journal oj  Physiology,  ijos.xxii,  p.  245. 


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COLUMBIA  UNIVERSITY 

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Lucas 
Physiological  and  pharmacological 
studies  of  the  ureter 


C.  U.  EI 


